Subsequent high blood pressure and hypertension by hypertensive disorders of pregnancy: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Hypertensive disorders of pregnancy can cause hypertension in the future. Understanding how the blood pressure values of women with and without hypertensive disorders of pregnancy differ will facilitate follow-up blood pressure monitoring in clinical settings. This study investigated the association between hypertensive disorders of pregnancy and subsequent high blood pressure and hypertension. This study used Japanese data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Follow-up systolic and diastolic blood pressures in normotensive women during pregnancy and those with hypertensive disorders of pregnancy were estimated using analysis of covariance adjusted for women with low birthweight, history of gestational diabetes mellitus, age, body mass index, pulse rate, smoking and drinking at the follow-up assessment, paternal hypertension history, and maternal hypertension or hypertensive disorders of pregnancy history. Finally, we performed a multiple logistic regression analysis. In total, 7343 women were included in the analysis. Women with a history of hypertensive disorders of pregnancy had higher blood pressure approximately three years postpartum compared with normotensive women. Hypertensive disorders of pregnancy in the most recent pregnancy in different subgroups, such as nulliparous women, multiparous women without a history of hypertensive disorders of pregnancy, and multiparous women with a history of hypertensive disorders of pregnancy, were associated with an increased risk of subsequent hypertension. Women's birthweight was also weakly associated with hypertension. Even one experience of hypertensive disorders of pregnancy may contribute to elevated blood pressure and hypertension approximately three years postpartum. In addition, women's birthweights may have a weak relationship with increasing blood pressure.

Associations between leisure time, non-leisure time physical activity, and kidney function in Japanese adults: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. METHODS: This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. RESULTS: The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (ß, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, ß, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and ß, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (ß, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables. CONCLUSIONS: We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function.

Genetic Risk, Lifestyle Adherence, and Risk of Developing Hyperuricaemia in a Japanese Population.

OBJECTIVE: To investigate the inter-relationships among genetic risk, healthy lifestyle adherence, and hyperuricaemia susceptibility. METHODS: This prospective cohort study was conducted with 7,241 hyperuricaemia-free individuals aged ≥ 20 years from the Tohoku Medical Megabank Community-based cohort study. A comprehensive lifestyle score included body mass index, smoking, drinking, and physical activity, and a polygenic risk score (PRS) was constructed based on uric acid loci from a previous genome-wide association study meta-analysis. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and hyperuricaemia incidence and calculate the area under the receiver operating characteristic curve (AUROC). Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dl or a self-reported history of hyperuricaemia. RESULTS: Of the 7,241 adults (80.7% females; mean [SD] age: 57.7 [12.6] years), 217 (3.0%) developed hyperuricaemia during 3.5 years of follow-up. Genetic risk correlated with hyperuricaemia development (P for interaction = 0.287), and lifestyle risks were independently associated. Those with a high genetic risk and poor lifestyle had the highest risk (odds ratio: 5.34; 95% confidence interval [CI]: 2.61-12.10). Although not statistically significant, incorporating the PRS in the model with lifestyle information improved predictive ability (AUROC = 0.771, 95% CI: 0.736-0.806 for lifestyle; AUROC = 0.785, 95% CI: 0.751-0.819 for lifestyle and PRS; p = 0.07). CONCLUSION: : A healthy lifestyle to prevent hyperuricaemia, irrespective of genetic risk, may mitigate the genetic risk. Genetic risk may complement lifestyle factors in identifying individuals at a heightened hyperuricaemia risk.

How Healthy Lifestyle Habits Have Interacted with SARS-CoV-2 Infection and the Effectiveness of COVID-19 Vaccinations: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Introduction: To examine the interaction between lifestyle habits and the COVID-19 vaccinations for preventing SARS-CoV-2 infection, we analyzed 11,016 adult participants registered in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Methods: Lifestyle variables, including regular exercise, smoking and drinking habits, sleep status, body mass index, and daily breakfast consumption, were assessed from 2014 to 2019 using baseline questionnaires. Information on SARS-CoV-2 infection and the COVID-19 vaccination were also collected from March 2020 to May 2023. The study period was divided into two in the postvaccination phase: the first period (the beginning of the vaccination program) and the second period (the fourth shot onward). Results: In the Cox proportional-hazards model analysis, the five-time vaccinations group showed a significantly lower risk of SARS-CoV-2 infection adjusted age, sex, underlying health condition, and lifestyle variables (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.76-0.86). Logistic regression analysis revealed that a higher number of vaccinations was significantly associated with a low risk of SARS-CoV-2 infection regardless of lifestyle habits (three times in the first period: odds ratio [OR] 0.19, 95% CI 0.15-0.24; five times in the second period: OR 0.07, 95% CI 0.05-0.11 vs. none). Regarding lifestyle habits, the risk reduction in those who had sleep satisfaction (OR 0.12, 95% CI 0.08-0.18) was slightly larger than in those who had sleep dissatisfaction (OR 0.23, 95% CI 0.17-0.32) in the group with the highest number of vaccinations in the first period; however, this interaction was hardly confirmed in the second period when the number of infected cases significantly increased. Conclusions: Our findings indicated that a higher number of COVID-19 vaccinations was associated with reduced risk of SARS-CoV-2 infection; otherwise, we may need to understand the advantages and limitations of a healthy lifestyle for preventing infection depending on the situation with vaccinations and infection spreading.

Trend analysis of pharmacist involvement in cancer care in Japan from 2015 to 2020: A nationwide survey study on hospital pharmacy practice.

INTRODUCTION: Pharmacists are needed as members of oncology teams. The Japanese Society of Hospital Pharmacists (JSHP) conducts a nationwide survey annually to analyze the actual situation and generate fundamental information about hospital pharmacy practice in Japan. Using data from this large-scale survey, we described pharmacists' involvement in cancer chemotherapy. We explored the factors related to the acceleration of pharmacists' tasks or involvement in clinical practice, primarily in oncology. METHODS: Data were obtained from annual surveys conducted by JSHP from 2015 to 2020. All variables were expressed as categorical variables and tabulated. The Chi-square and Fisher's exact tests were used to compare the categorical variables. The Cochran-Armitage trend test was used to identify significant trends. RESULTS: From 2015 to 2020, 22,362 responses were recorded. After applying the exclusion criteria, 20,906 were analyzed. The proportion of hospitals enrolling pharmacists with oncology-related certifications significantly increased in all hospitals providing cancer care. Multivariable logistic regression analysis indicated that a smaller number of beds per pharmacist significantly correlated with additional fees for outpatient pharmacy services (p = 0.0002 for trend). CONCLUSION: Hospitals charging increased fees for outpatient oncology pharmacy services were associated with a smaller number of beds per pharmacist, regardless of hospital size. A balance between the number of beds and pharmacists, particularly certified oncology pharmacists, is crucial for safe and high-quality cancer treatment.

Predicting EGFR Status After Radical Nephrectomy or Partial Nephrectomy for Renal Cell Carcinoma on CT Using a Self-attention-based Model: Variable Vision Transformer (vViT).

OBJECTIVE: To assess the effectiveness of the vViT model for predicting postoperative renal function decline by leveraging clinical data, medical images, and image-derived features; and to identify the most dominant factor influencing this prediction. MATERIALS AND METHODS: We developed two models, eGFR10 and eGFR20, to identify patients with a postoperative reduction in eGFR of more than 10 and more than 20, respectively, among renal cell carcinoma patients. The eGFR10 model was trained on 75 patients and tested on 27, while the eGFR20 model was trained on 77 patients and tested on 24. The vViT model inputs included class token, patient characteristics (age, sex, BMI), comorbidities (peripheral vascular disease, diabetes, liver disease), habits (smoking, alcohol), surgical details (ischemia time, blood loss, type and procedure of surgery, approach, operative time), radiomics, and tumor and kidney imaging. We used permutation feature importance to evaluate each sector's contribution. The performance of vViT was compared with CNN models, including VGG16, ResNet50, and DenseNet121, using McNemar and DeLong tests. RESULTS: The eGFR10 model achieved an accuracy of 0.741 and an AUC-ROC of 0.692, while the eGFR20 model attained an accuracy of 0.792 and an AUC-ROC of 0.812. The surgical and radiomics sectors were the most influential in both models. The vViT had higher accuracy and AUC-ROC than VGG16 and ResNet50, and higher AUC-ROC than DenseNet121 (p < 0.05). Specifically, the vViT did not have a statistically different AUC-ROC compared to VGG16 (p = 1.0) and ResNet50 (p = 0.7) but had a statistically different AUC-ROC compared to DenseNet121 (p = 0.87) for the eGFR10 model. For the eGFR20 model, the vViT did not have a statistically different AUC-ROC compared to VGG16 (p = 0.72), ResNet50 (p = 0.88), and DenseNet121 (p = 0.64). CONCLUSION: The vViT model, a transformer-based approach for multimodal data, shows promise for preoperative CT-based prediction of eGFR status in patients with renal cell carcinoma.

Genetic Risk, Healthy Lifestyle Adherence, and Risk of Developing Diabetes in the Japanese Population.

AIM: This study examined the relationship between genetic risk, healthy lifestyle, and risk of developing diabetes. METHODS: This prospective cohort study included 11,014 diabetes-free individuals ≥ 20 years old from the Tohoku Medical Megabank Community-based cohort study. Lifestyle scores, including the body mass index, smoking, physical activity, and gamma-glutamyl transferase (marker of alcohol consumption), were assigned, and participants were categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score (PRS) was constructed based on the type 2 diabetes loci from the BioBank Japan study. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and diabetes incidence and to calculate the area under the receiver operating characteristic curve (AUROC). RESULT: Of the 11,014 adults included (67.8% women; mean age [standard deviation], 59.1 [11.3] years old), 297 (2.7%) developed diabetes during a mean 4.3 (0.8) years of follow-up. Genetic and lifestyle score is independently associated with the development of diabetes. Compared with the low genetic risk and ideal lifestyle groups, the odds ratio was 3.31 for the low genetic risk and poor lifestyle group. When the PRS was integrated into a model including the lifestyle and family history, the AUROC significantly improved to 0.719 (95% confidence interval [95% CI]: 0.692-0.747) compared to a model including only the lifestyle and family history (0.703 [95% CI, 0.674-0.732]). CONCLUSION: Our findings indicate that adherence to a healthy lifestyle is important for preventing diabetes, regardless of genetic risk. In addition, genetic risk might provide information beyond lifestyle and family history to stratify individuals at high risk of developing diabetes.

Predicting isocitrate dehydrogenase status among adult patients with diffuse glioma using patient characteristics, radiomic features, and magnetic resonance imaging: Multi-modal analysis by variable vision transformer.

OBJECTIVES: To evaluate the performance of the multimodal model, termed variable Vision Transformer (vViT), in the task of predicting isocitrate dehydrogenase (IDH) status among adult patients with diffuse glioma. MATERIALS AND METHODS: vViT was designed to predict IDH status using patient characteristics (sex and age), radiomic features, and contrast-enhanced T1-weighted images (CE-T1WI). Radiomic features were extracted from each enhancing tumor (ET), necrotic tumor core (NCR), and peritumoral edematous/infiltrated tissue (ED). CE-T1WI were split into four images and input to vViT. In the training, internal test, and external test, 271 patients with 1070 images (535 IDH wildtype, 535 IDH mutant), 35 patients with 194 images (97 IDH wildtype, 97 IDH mutant), and 291 patients with 872 images (436 IDH wildtype, 436 IDH mutant) were analyzed, respectively. Metrics including accuracy and AUC-ROC were calculated for the internal and external test datasets. Permutation importance analysis combined with the Mann-Whitney U test was performed to compare inputs. RESULTS: For the internal test dataset, vViT correctly predicted IDH status for all patients. For the external test dataset, an accuracy of 0.935 (95% confidence interval; 0.913-0.945) and AUC-ROC of 0.887 (0.798-0.956) were obtained. For both internal and external test datasets, CE-T1WI ET radiomic features and patient characteristics had higher importance than other inputs (p < 0.05). CONCLUSIONS: The vViT has the potential to be a competent model in predicting IDH status among adult patients with diffuse glioma. Our results indicate that age, sex, and CE-T1WI ET radiomic features have key information in estimating IDH status.

Associations between housing and psychological damage by earthquake and modifiable risk factors for dementia in general older adults: Tohoku Medical Megabank community-based cohort study.

AIM: To evaluate the association between housing and psychological damage caused by the Great East Japan Earthquake (GEJE) and modifiable risk factors (MRFs) of dementia for general population of older adults. METHODS: This cross-sectional study enrolled 29 039 community-dwelling older adults (mean age 69.1 ± 2.9 years, 55.5% women). We evaluated disaster-related damage (by complete or not complete housing damage) and psychological damage (by post-traumatic stress reaction [PTSR]) after the GEJE using a self-report questionnaire. MRFs encompassed the presence of depression, social isolation, physical inactivity, smoking, and diabetes. We examined the association between disaster-related damage and MRFs using ordinary least squares and modified Poisson regression models adjusted for sociodemographic and health status variables. RESULTS: Complete housing damage and PTSR were identified in 2704 (10.0%) and 855 (3.2%) individuals, respectively. The number of MRFs was significantly larger for the individuals with complete housing damage (ß = 0.23; 95% confidence interval [CI]: 0.19-0.27) and PTSR (ß = 0.60; 95% CI: 0.53-0.67). Prevalence ratios (PRs) for depression and physical inactivity were higher in individuals with complete housing damage. The PRs for all domains of the MRFs were significantly higher in individuals with PTSR. CONCLUSIONS: Housing and psychological damage caused by the GEJE were associated with an increased risk factor of dementia. To attenuate the risk of dementia, especially among older victims who have experienced housing and psychological damage after a disaster, multidimensional support across various aspects of MRFs is required. Geriatr Gerontol Int 2024; 24: 509-516.

Identifying key factors for predicting O6-Methylguanine-DNA methyltransferase status in adult patients with diffuse glioma: a multimodal analysis of demographics, radiomics, and MRI by variable Vision Transformer.

PURPOSE: This study aimed to perform multimodal analysis by vision transformer (vViT) in predicting O6-methylguanine-DNA methyl transferase (MGMT) promoter status among adult patients with diffuse glioma using demographics (sex and age), radiomic features, and MRI. METHODS: The training and test datasets contained 122 patients with 1,570 images and 30 patients with 484 images, respectively. The radiomic features were extracted from enhancing tumors (ET), necrotic tumor cores (NCR), and the peritumoral edematous/infiltrated tissues (ED) using contrast-enhanced T1-weighted images (CE-T1WI) and T2-weighted images (T2WI). The vViT had 9 sectors; 1 demographic sector, 6 radiomic sectors (CE-T1WI ET, CE-T1WI NCR, CE-T1WI ED, T2WI ET, T2WI NCR, and T2WI ED), 2 image sectors (CE-T1WI, and T2WI). Accuracy and area under the curve of receiver-operating characteristics (AUC-ROC) were calculated for the test dataset. The performance of vViT was compared with AlexNet, GoogleNet, VGG16, and ResNet by McNemar and Delong test. Permutation importance (PI) analysis with the Mann-Whitney U test was performed. RESULTS: The accuracy was 0.833 (95% confidence interval [95%CI]: 0.714-0.877) and the area under the curve of receiver-operating characteristics was 0.840 (0.650-0.995) in the patient-based analysis. The vViT had higher accuracy than VGG16 and ResNet, and had higher AUC-ROC than GoogleNet (p<0.05). The ED radiomic features extracted from the T2-weighted image demonstrated the highest importance (PI=0.239, 95%CI: 0.237-0.240) among all other sectors (p<0.0001). CONCLUSION: The vViT is a competent deep learning model in predicting MGMT status. The ED radiomic features of the T2-weighted image demonstrated the most dominant contribution.

Association between Maternal Birth Weight and Prevalence of Congenital Malformations in Offspring: The Japanese Environment and Children's Study.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of <2500 g (low MBW) was associated with an increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075-1.792]), angioma (1.491 [1.079-2.059]), and inguinal hernia (1.746, [1.189-2.565]), while those with an MBW of ≥4000 g (high MBW) were associated with congenital anomalies of the urinary tract (2.194, [1.261-3.819]) and arrhythmia (1.775, [1.157-2.725]) compared with those with an MBW of 3000-3499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052-2.064]), congenital heart disease (1.615, [1.119-2.332]), genital organs (1.648, [1.130-2.405]), hypospadias (1.804, [1.130-2.881]), and inguinal hernia (1.484, [1.189-1.851]) in male infants and CAKUT (1.619, [1.154-2.273]) in female infants, whereas high MBW was associated with congenital heart disease (1.745, [1.058-2.877]) and CAKUT (2.470, [1.350-4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.

Relationship between traditional risk factors for hypertension and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study.

Risk factors for hypertension have been emphasized in the Japanese Society of Hypertension Guidelines for the Management of Hypertension. However, large-scale studies on the association of smoking, potassium excretion, and gamma-glutamyl transferase level with BP in the Japanese population are limited. We conducted a cross-sectional study to examine the association between hypertension risk factors and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study (23,446 men and 38,921 women aged ≥20 years). A model adjusted for age, body mass index, smoking status, drinking status, estimated daily salt intake, potassium excretion, (or urinary sodium-to-potassium ratio), gamma-glutamyl transferase, physical activity, education level, status of damage to homes during the Great East Japan Earthquake, and residential areas was used. The average age and systolic blood pressure were 62.5 (10.3) years for men and 59.6 (11.3) years for women, 128.9 (16.7) mmHg for men and 124.7 (17.5) mmHg for women, respectively. Body mass index estimated daily salt intake, urinary sodium-to-potassium ratio and gamma-glutamyl transferase levels were positively associated with systolic blood pressure. Compared with never-drinkers, current drinkers who consumed 23-45 g/day and ≥46.0 g/day had significantly increased systolic blood pressure. Conversely, current smokers (1-10 cigarettes/day and 11-20 cigarettes/day) were inversely associated with systolic blood pressure compared to never-smokers. Overall, systolic blood pressure was associated with gamma-glutamyl transferase and hypertension risk factors, including body mass index, alcohol consumption, estimated daily salt intake, urinary sodium-to-potassium ratio, and potassium excretion. Our findings support the notion that lifestyle modifications should be attempted to prevent hypertension.

The Population-Attributable Fractions of Small-for-Gestational-Age Births: Results from the Japan Birth Cohort Consortium.

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42-2.09]), gestational weight gain (1.95 [1.61-2.38]), and continued smoking during pregnancy (1.59 [1.01-2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6-15.1%], 31.4% [22.1-39.6%], and 3.2% [-4.8-10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Long-term prognosis and clinical practice for new-onset ulcerative colitis in the era of biologics: A Japanese retrospective study.

Background and Aim: There is a scarcity of data on long-term outcomes in patients with new-onset ulcerative colitis (UC) in the era of biologics. We aimed to clarify the long-term prognosis of UC and the clinical practice of prescriptions for UC. Methods: We collected 6689 new-onset UC cases using a medical claim database provided by DeSC Healthcare, Inc. We investigated the surgery-free, systemic steroid-free, and molecular targeting drug-free rates and compared their differences based on UC-onset age. We used multivariate analysis to identify clinical factors affecting long-term prognosis and investigated the transition of prescriptions for UC. Results: The surgery-free, systemic steroid-free, and molecular targeting drug-free rates at 5 years post-UC diagnosis were 98.5%, 61.0%, and 88.7%, respectively. Pediatric patients had higher surgery-free rates compared with elderly patients and non-pediatric/non-elderly patients (P = 0.022), whereas the systemic steroid-free and molecular targeting drug-free rates were significantly lower (P< 0.0001, P < 0.0001, respectively). The retention rate of the first molecular targeting drug did not differ between drugs. The prescription rates of systemic steroid, immunomodulator, and molecular targeting drug increased from the second quarter in 2014 to the fourth quarter in 2021 (29.8%-39.1%, 6.8%-17.7%, and 7.6%-16.4%, respectively). Conclusions: We clarified the long-term prognosis and clinical practice of new-onset UC cases. The long-term outcome after UC onset might improve because of increasing use of new therapeutic agents. Further investigations are warranted.

Identification of Risk Factors for Mortality and Prolonged Hospitalization in Patients Treated With Surgical Drainage for Otogenic Intracranial Complications: A Nationwide Study Using a Japanese Inpatient Database.

OBJECTIVE: Data on risk factors for otogenic intracranial complications including cerebral abscess have been limited. Using a nationwide database, the aim was to identify the factors related to mortality and delayed discharge. STUDY DESIGN: Retrospective. SETTING: Nationwide database using the Diagnostic Procedure Combination database. MAIN OUTCOME MEASURES: Data of 145 patients were extracted from a Japanese inpatient database between 2012 and 2020. The main outcome was survival at discharge. In a subgroup analysis of the 137 surviving patients, the second outcome was delayed discharge. RESULTS: The mortality rate was 5.5% (8 of 145). Logistic regression analyses identified intracerebral complications (adjusted odds ratio [OR], 3.09) and more than 2-day delay of the first surgery after admission (adjusted OR, 4.68) as risk factors for mortality. Specifically, consciousness level evaluated by the Japan Coma Scale (JCS) was significantly related to prolonged hospitalization or mortality: JCS I (adjusted OR, 3.40) and JCS ≥II (adjusted OR, 25.1). CONCLUSIONS: Although otogenic intracranial complications are rare, and their mortality is decreasing because of the progress in imaging and clinical strategies, they remain the most severe complications of suppurative otitis media and/or cholesteatoma. Consciousness level at admission, comorbid diabetes mellitus, and a greater than 2-day delay of surgical intervention were related to prolonged hospitalization or mortality.

Efficacy of exponentiation method with a convolutional neural network for classifying lung nodules on CT images by malignancy level.

OBJECTIVES: The aim of this study was to examine the performance of a convolutional neural network (CNN) combined with exponentiating each pixel value in classifying benign and malignant lung nodules on computed tomography (CT) images. MATERIALS AND METHODS: Images in the Lung Image Database Consortium-Image Database Resource Initiative (LIDC-IDRI) were analyzed. Four CNN models were then constructed to classify the lung nodules by malignancy level (malignancy level 1 vs. 2, malignancy level 1 vs. 3, malignancy level 1 vs. 4, and malignancy level 1 vs. 5). The exponentiation method was applied for exponent values of 1.0 to 10.0 in increments of 0.5. Accuracy, sensitivity, specificity, and area under the curve of receiver operating characteristics (AUC-ROC) were calculated. These statistics were compared between an exponent value of 1.0 and all other exponent values in each model by the Mann-Whitney U-test. RESULTS: In malignancy 1 vs. 4, maximum test accuracy (MTA; exponent value = 2.0, 3.0, 3.5, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, and 10.0) and specificity (6.5, 7.0, and 9.0) were improved by up to 0.012 and 0.037, respectively. In malignancy 1 vs. 5, MTA (6.5 and 7.0) and sensitivity (1.5) were improved by up to 0.030 and 0.0040, respectively. CONCLUSIONS: The exponentiation method improved the performance of the CNN in the task of classifying lung nodules on CT images as benign or malignant. The exponentiation method demonstrated two advantages: improved accuracy, and the ability to adjust sensitivity and specificity by selecting an appropriate exponent value. CLINICAL RELEVANCE STATEMENT: Adjustment of sensitivity and specificity by selecting an exponent value enables the construction of proper CNN models for screening, diagnosis, and treatment processes among patients with lung nodules. KEY POINTS: • The exponentiation method improved the performance of the convolutional neural network. • Contrast accentuation by the exponentiation method may derive features of lung nodules. • Sensitivity and specificity can be adjusted by selecting an exponent value.

The prevalence of end-of-life chemotherapy and targeted therapy in Japan, assessed using a health claims database.

PURPOSE: This study aimed to investigate the current status of end-of-life chemotherapy and targeted therapy and explore the aggressiveness of end-of-life care in Japan using the DeSC database, a large administrative claims database. METHODS: We identified fatal cases of at least one cancer-related diagnosis between April 2015 and November 2020. Patients prescribed at least one anticancer drug were analyzed, and chemotherapy regimens were categorized based on the combination of concomitant anticancer drugs prescribed. RESULTS: Among 1,095,713 individuals enrolled in the National Health Insurance database, 7,300 deaths with cancer-related diagnosis were identified. Of these, 4,010 cases were identified in which at least one anticancer drug was prescribed, and 11.6% of 7,300 death had been prescribed anticancer drugs in their last 30 days of life. The most commonly used regimen was S-1 (tegafur, gimeracil, and oteracil potassium combination) monotherapy, followed by nivolumab monotherapy and nab-paclitaxel plus gemcitabine. Immune checkpoint inhibitor monotherapy was more likely prescribed to patients whose last chemotherapy dose was in the last 30 days of life (p = 0.0066, chi-squared test). CONCLUSIONS: This study provides insights into the current status of end-of-life chemotherapy and targeted therapy in Japan, using a large administrative claims database. The results of this study will inform future research on end-of-life chemotherapy and targeted therapy, and help develop strategies to improve the quality of life of patients with advanced cancer.

Association between low levels of anti-inflammatory cytokines during pregnancy and postpartum depression.

AIM: Previous studies based on a relatively limited number of subjects have indicated potential associations between plasma cytokine concentrations in perinatal women and postpartum depression (PPD). This report aimed to examine alterations in cytokine levels during pregnancy and after delivery by measuring nine cytokines in prenatal and postnatal plasma samples in a large cohort. METHODS: A nested, case-control study was conducted using plasma samples from 247 women with PPD (Edinburgh Postnatal Depression Scale: EPDS ≥9) and 243 age-matched control (EPDS ≤2) women from among perinatal women who participated in the Tohoku Medical Megabank three-generation cohort. Concentrations of nine plasma cytokines (IFN-γ, IL-1ß, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, and TNF-α) in plasma collected at the time of enrollment during pregnancy and 1 month after delivery were determined using an immunoassay kit. RESULTS: Cross-sectional comparisons of cytokine levels during pregnancy and after delivery indicated that the PPD group maintained significantly lower plasma IL-4 levels during pregnancy and after delivery than the control group, and that plasma IL-4 levels decreased significantly during pregnancy regardless of PPD status. Plasma IL-10 levels were significantly higher during pregnancy than after delivery only among healthy controls, and plasma IL-10 levels were significantly higher in the control group than in the PPD group. Moreover, IFN-γ, IL-6, IL-12p40, and TNF-α levels were significantly lower during pregnancy compared with after delivery regardless of PPD status. CONCLUSIONS: These results suggest a potential protective effect of the anti-inflammatory cytokines IL-4 and IL-10 during pregnancy against the development of PPD.

Association between being Overweight in Young Childhood and during School Age and Puberty.

To examine whether body type at birth, body weight, and obesity in early childhood are associated with overweight/obesity during school age and puberty. Data from maternal and child health handbooks, baby health checkup information, and school physical examination information of participants at birth and three-generation cohort studies were linked. Association between body type and body weight at different time intervals (at birth and at 1.5, 3.5, 6, 11, and 14 years of age) were comprehensively analyzed using a multivariate regression model adjusted for gender, maternal age at childbirth, maternal parity, and maternal body mass index, and drinking and smoking statuses at pregnancy confirmation. Children who are overweight in young childhood had a greater risk of being overweight. Particularly, overweight at one year of age during checkup was associated with overweight at 3.5 years (adjusted odds ratio (aOR), 13.42; 95% confidence interval (CI), 4.46-45.42), 6 years (aOR, 6.94; 95% CI, 1.64-33.46), and 11 years (aOR, 5.22; 95% CI, 1.25-24.79) of age. Therefore, being overweight in young childhood could increase the risk of being overweight and obese during school age and puberty. Early intervention in young childhood may be warranted to prevent obesity during school age and puberty.

Associations of Education and Income with Secondhand Smoke Exposure Among Non-smoking Pregnant Women in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

OBJECTIVES: There is accumulating evidence that lower socioeconomic groups are more exposed to secondhand smoke (SHS) than higher ones in the general population. The objective of the study was to examine the associations of education and income with SHS exposure among non-smoking pregnant women in Japan. METHODS: We analyzed data from 11,615 non-smoking pregnant women in Japan who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. SHS exposure was defined as indoor exposure to someone else's cigarette smoke ≥ 1 day/week during pregnancy. Multiple logistic regression analyses were conducted to examine whether pregnant women's educational attainment or equivalent household income was associated with SHS exposure, adjusting for covariates. Stratified analyses by work status were also conducted. RESULTS: The prevalence of SHS exposure during pregnancy was 32.6%; 27.6% among non-working women and 35.8% among working women. Lower educational attainment was associated with an increased risk of SHS exposure; the odds ratio of high school education or lower compared with university education or higher was 1.87 (95% confidence interval, 1.66-2.10). Lower equivalent household income was associated with an increased risk of SHS exposure; the odds ratio of the lowest compared with the highest level of income was 1.53 (95% confidence interval, 1.35-1.74). These associations did not differ between non-working women and working women. CONCLUSIONS FOR PRACTICE: Associations of education and income with SHS exposure imply that educational interventions and financial incentives are needed for pregnant women and their household smokers.